title: Dendritic cell targeted liposomes-protamine-DNA complexes mediated by synthetic mannosylated cholesterol as a potential carrier for DNA vaccine.
abstract: To construct mannosylated liposomes/protamine/DNA (LPD) carriers for DNA vaccine targeting to dendritic cells (DCs), a mannosylated cholesterol derivative (Man-C6-Chol) was synthesized via simple ester linkage and amide bonds. Then, the Man-C6-Chol was applied to LPD formulation as a synthetic ligand. The physicochemical properties of mannosylated LPD (Man-LPD) were first evaluated, including the size and zeta potential, morphology and the ability to protect DNA against DNase I degradation. Man-LPD showed a small size with a stable viral-like structure. In comparison to non-mannose liposomes/LPD (Man-free liposomes/LPD), mannosylated liposomes/LPD (Man-liposomes/Man-LPD) exhibited higher efficiency in both intracellular uptake (2.3-fold) and transfection (4.5-fold) in vitro. Subsequent MTT assays indicated that the LPD carriers had low toxicity on the tested cells. Afterwards, the investigation into the maturation activation on primary bone marrow-derived DCs (BMDCs) showed that both Man-LPD and Man-free LPD induced remarkable up-regulation of CD80, CD86 and CD40 on BMDCs. Inspired by these studies, we can conclude that the synthetic mannosylated LPD targeting to DCs was a potential carrier for DNA vaccine.
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
authors.forename: Pan
authors.initials: P
authors.lastname: Li
authors.forename: Simu
authors.initials: S
authors.lastname: Chen
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jiayu
authors.initials: J
authors.lastname: Jiang
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011479:Protamines / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D008081:Liposomes; D011479:Protamines; D019444:Vaccines, DNA; D002784:Cholesterol; D008358:Mannose